Elbasvir and Grazoprevir

Elbasvir and grazoprevir, sold together as Zepatier, are approved to treat the following:

• Zepatier treats chronic hepatitis C virus (HCV) genotype 1 (subtypes 1a and 1b) infection in adults and children 12 years of age and older or weighing at least 30 kg
• Zepatier treats chronic hepatitis C virus (HCV) genotype 4 infection in the same age and weight group
• Zepatier is used for people who have never been treated for HCV (treatment-naïve) and for those who have tried prior treatments including peginterferon plus ribavirin (PegIFN/RBV), with or without an HCV protease inhibitor
• Zepatier is approved for use in patients who also have HIV-1 co-infection, following genotype-based dosing guidelines
• Zepatier can be used in patients with any degree of kidney disease, including those receiving hemodialysis
• In certain patient populations, Zepatier is used in combination with ribavirin (an additional antiviral); genotype 1a with certain resistance mutations and genotype 4 patients with prior treatment experience are examples

Zepatier combines two direct-acting antivirals that block the hepatitis C virus from making copies of itself. Elbasvir targets a viral protein called NS5A, which the virus needs to replicate its genetic material and assemble new virus particles. Grazoprevir targets NS3/4A protease, an enzyme the virus uses to process its own proteins into working parts. Blocking both at once makes it very difficult for HCV to reproduce and spread.

Because the two drugs attack different steps in the viral life cycle, they work together more powerfully than either would alone — and this combination strategy helps reduce the chance that the virus develops resistance to the treatment.

Zepatier is taken as one tablet by mouth once a day. It can be taken with or without food — a meal will not meaningfully change how the medicine works. Treatment length is either 12 or 16 weeks, determined by your HCV genotype, whether you have certain viral resistance mutations, and your prior treatment history.

• Some patients take Zepatier alone; others take it with ribavirin — your prescriber will specify this
• Blood tests to check your liver are required before treatment starts, at week 8, and (for 16-week courses) at week 12
• No dose adjustment is needed for kidney disease, including hemodialysis
• Zepatier is not for people with moderate or severe liver impairment (Child-Pugh B or C)

Most people tolerate Zepatier well — the majority of reported side effects in clinical trials were mild. Common ones include:

Contact your doctor right away if you develop yellowing of the skin or eyes, severe fatigue, loss of appetite, vomiting, dark urine, or pale stools — these could be signs of serious liver inflammation or hepatitis B reactivation, which require prompt medical attention.

• Hepatitis B reactivation: This is the most serious risk. If you have hepatitis B (even an old, seemingly resolved infection), treating hepatitis C with Zepatier can trigger the hepatitis B virus to become active again — sometimes causing severe liver failure and death. You must be tested for HBV before starting, and co-infected patients need monitoring throughout and after treatment.
• Liver enzyme (ALT) elevations: About 1% of patients develop significant rises in liver enzymes, typically after week 8 of treatment. Women, older adults, and people of Asian descent have a slightly higher risk. Regular blood tests are required to catch this early. In most cases, levels normalize on their own, but Zepatier may need to be stopped if elevations are severe.
• Liver decompensation/failure: Patients with advanced liver disease (cirrhosis or prior liver failure) face a risk of sudden liver deterioration. Zepatier is contraindicated in moderate-to-severe liver impairment. Watch for jaundice, fluid buildup in the abdomen, confusion, or vomiting blood.
• Drug interactions: Several common medicines can either make Zepatier ineffective or cause dangerously high drug levels — always do a full medication review before starting.

Zepatier has significant interactions with many medicines. Always tell your doctor and pharmacist everything you take — including herbs and supplements — before starting.

• Rifampin, phenytoin, carbamazepine, St. John's Wort, efavirenz — contraindicated; these lower Zepatier levels enough to make it stop working
• Certain HIV medicines (atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cobicistat-containing regimens) — contraindicated or not recommended; they raise grazoprevir to levels that can harm your liver
• Cyclosporine (immunosuppressant) — contraindicated; dangerously increases grazoprevir exposure
• Statins (atorvastatin, rosuvastatin, fluvastatin, lovastatin, simvastatin) — dose limits apply; Zepatier raises statin levels, increasing the risk of muscle damage (myopathy)
• Tacrolimus (transplant medicine) — blood levels of tacrolimus must be monitored closely during Zepatier treatment
• Bosentan, nafcillin, etravirine, modafinil, oral ketoconazole — not recommended; may reduce Zepatier effectiveness or raise its levels
• Diabetes medicines — clearing HCV can improve liver function and change how your body handles blood sugar; dose adjustments of diabetes medicines may be needed
• Warfarin — INR (a blood clotting measure) should be monitored, as liver function changes can affect warfarin activity

Not a complete list. The label covers the interactions the manufacturer studied or reported, and our own interaction database does not cover every medicine either. Bring your full medication list, including vitamins and herbal products, to your pharmacist.

• Hepatitis B history: You must be tested for hepatitis B (HBsAg and anti-HBc) before starting — Zepatier can reactivate HBV, sometimes fatally
• Moderate or severe liver impairment (Child-Pugh B or C) or prior liver decompensation: Zepatier is contraindicated — do not take it
• Pregnancy: No adequate human safety data exist for Zepatier alone; if taken with ribavirin, the combination is contraindicated during pregnancy and effective contraception is required
• Breastfeeding: It is not known if Zepatier passes into human breast milk; discuss risks and benefits with your doctor
• Children under 12 or weighing less than 30 kg: Safety and effectiveness have not been established
• Older adults (65+): Drug levels may be somewhat higher, and there is a slightly elevated risk of liver enzyme elevations — no dose change is needed, but monitoring is important
• Women and people of Asian descent: May have higher drug levels and slightly higher risk of liver enzyme elevations; standard monitoring applies, no dose adjustment needed
• Kidney disease / hemodialysis: No Zepatier dose adjustment is needed, but ribavirin (if added) may need to be adjusted — refer to ribavirin's prescribing information
• Liver transplant recipients or those awaiting transplant: Safety and effectiveness have not been established

There is limited information on what happens if someone takes too much Zepatier. There is no specific antidote. If an overdose occurs, the recommended approach is to monitor the person for any symptoms and treat them supportively.

Because elbasvir and grazoprevir bind very tightly to proteins in the blood, hemodialysis (dialysis) will not effectively remove them from the body.

Zepatier acts directly on the hepatitis C virus rather than on the immune system. Both elbasvir and grazoprevir have been studied for their effect on heart rhythm (QT interval): even at concentrations far above therapeutic levels, neither drug causes clinically meaningful changes in heart electrical activity. The drugs do not appear to carry a meaningful risk of abnormal heart rhythms at prescribed doses.

After taking Zepatier by mouth, peak concentrations are reached within about 2–3 hours. Both drugs are extensively bound to proteins in the blood (over 98%) and distribute widely in the body, with both concentrating particularly in the liver. They are primarily broken down by a liver enzyme called CYP3A and are eliminated mostly through the feces (over 90%); less than 1% exits through urine. The half-lives — how long it takes the body to clear half of the drug — are roughly 24 hours for elbasvir and 31 hours for grazoprevir, which is why once-daily dosing works well. Zepatier can be taken with or without food, as food causes only minor changes in absorption that are not clinically meaningful.

Store ZEPATIER in the original blister package until use to protect from moisture. Store ZEPATIER at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (between 59°F to 86°F) .